Jerusalem's CoVID-19 Experience-The Effect of Ethnicity on Disease Prevalence and Adherence to Testing.

BACKGROUND: The management of the SARS-CoV-2 pandemic depends amongst other factors on disease prevalence in the general population. The gap between the true rate of infection and the detected rate of infection may vary, especially between sub-groups of the population. Identifying subpopulations with high rates of undetected infection can guide authorities to direct resource distribution in order to improve health equity. METHODS: A cross-sectional epidemiological survey was conducted between April and July 2021 in the Pediatric Emergency Department of the Shaare Zedek Medical Center, Jerusalem, Israel. We compared three categories: unconfirmed disease (UD), positive serology test result with no history of positive PCR; confirmed disease (CD), history of a positive PCR test result, regardless of serology test result; and no disease (ND), negative serology and no history of PCR. These categories were applied to local prevailing subpopulations: ultra-orthodox Jews (UO), National Religious Jews (NRJ), secular Jews (SJ), and Muslim Arabs (MA). RESULTS: Comparing the different subpopulations groups, MAs and UOs had the greatest rate of confirmed or unconfirmed disease. MA had the highest rate of UD and UO had the highest rate of CD. UD significantly correlated with ethnicity, with a low prevalence in NRJ and SJ. UD was also associated with larger family size and housing density defined as family size per number of rooms. CONCLUSION: This study highlights the effect of ethnicity on disease burden. These findings should serve to heighten awareness to disease burden in weaker populations and direct a suitable prevention program to each subpopulation's needs. Early awareness and possible intervention may lower morbidity and mortality.

Acute glomerulonephritis with concurrent suspected bacterial pneumonia - is it the tip of the iceberg?

BACKGROUND: Post infectious glomerulonephritis is the most common glomerulopathy in children, occurring several weeks after nephritogenic streptococcal throat or skin infection. Reports of acute glomerulonephritis (AGN) occurring during active bacterial pneumonia in children are rare. The aim of this study was to evaluate the incidence of AGN concurrent with bacterial pneumonia in children. METHODS: We reviewed records of all children admitted with a diagnosis of pneumonia to the pediatric department in a single tertiary medical center between January 2015 and April 2023. Patients with bacterial pneumonia and concurrent glomerulonephritis were included. RESULTS: Eleven (0.98%) of 1,123 patients with bacterial pneumonia had concurrent AGN. All were males with a median age of 2.7 years (range 1-13). Mean time from bacterial pneumonia onset to acute glomerulonephritis symptoms was 2.7 ± 1.5 days. Five (45%) patients had evidence of pneumococcal infection. Hypertension was found in 10 (91%) patients. Mean trough eGFR was 43.5 ± 21.4 ml/min/1.73 m2 (range 11-73). Ten patients (91%) had low C3 levels. Median urinary protein-to-creatinine ratio was 2.5 mg/mg (IQR 2.15-14.75). All patients fully recovered. Microscopic hematuria was the last finding to normalize after a median of 29.5 days (IQR 17.25-38). CONCLUSION: AGN during bacterial pneumonia may be more frequent than previously recognized. Kidney prognosis was excellent in all patients. Prospective studies are needed to evaluate the impact of this condition.

Dynamics of invasive pneumococcal disease in infants < 2 years old following PCV7/13 implementation using two infant and a booster dose schedule: evidence for indirect protection of young infants, Israel, 2004 to 2019.

BackgroundPneumococcal conjugated vaccine (PCV)7 and PCV13 programmes started in Israel from July 2009 and November 2010 respectively, with a 2+1 schedule (one dose at 2 months old, one at 4 months old, and a booster dose at 12 months old). Thereafter, invasive pneumococcal disease (IPD) rates substantially declined in children. Uptake of all three doses in < 2-year-olds since 2012 is > 90%. For still incompletely vaccinated infants (≤ 12 months old), how well the PCV 2+1 programme shields from IPD is not fully resolved.AimTo assess the adequacy of protection conferred by the 2+1 schedule PCV vaccination programme, particularly among incompletely-vaccinated infants.MethodsThis was a population-based, prospective, nationwide active IPD surveillance study in Israel, 2004-2019, in children < 24 months old. We estimated annual incidence rates (IR) of overall IPD, IPD caused by PCV13 serotypes (VT13), and non-PCV13 serotypes (NVT13). Annual IPD IRs were stratified by age: < 4 months (receiving ≤ 1 dose), 4-6 months (immediately post dose 2), 7-12 months (a few months post dose 2), and 13-23 months (post dose 3). Late-PCV (2004-2008) to pre-PCV13 (2016-2019) mean annual IR ratios (IRRs) were calculated.Results2,569 IPD episodes were recorded. VT13 decreased > 90% in all age groups, while NVT13 seemed to increase. All-IPD rates declined in all age groups by 56-70%. The 2+1 schedule impact on 7-12-month-old infants (pre-booster) was similar to that on 13-23-month-old children (post booster), with PCV13 IPD reductions of 97% and 98%, respectively.ConclusionsIndirect (herd) protection of infants, including < 4 month-olds with ≤ 1 PCV dose, was achieved by the 2+1 PCV schedule programme which thus seems adequate.

Whole-Genome Sequencing Reveals Differences among Kingella kingae Strains from Carriers and Patients with Invasive Infections.

As a result of the increasing use of sensitive nucleic acid amplification tests, Kingella kingae is being recognized as a common pathogen of early childhood, causing medical conditions ranging from asymptomatic oropharyngeal colonization to bacteremia, osteoarthritis, and life-threatening endocarditis. However, the genomic determinants associated with the different clinical outcomes are unknown. Employing whole-genome sequencing, we studied 125 international K. kingae isolates derived from 23 healthy carriers and 102 patients with invasive infections, including bacteremia (n = 23), osteoarthritis (n = 61), and endocarditis (n = 18). We compared their genomic structures and contents to identify genomic determinants associated with the different clinical conditions. The mean genome size of the strains was 2,024,228 bp, and the pangenome comprised 4,026 predicted genes, of which 1,460 (36.3%) were core genes shared by >99% of the isolates. No single gene discriminated between carried and invasive strains; however, 43 genes were significantly more frequent in invasive isolates, compared to asymptomatically carried organisms, and a few showed a significant differential distribution among isolates from skeletal system infections, bacteremia, and endocarditis. The gene encoding the iron-regulated protein FrpC was uniformly absent in all 18 endocarditis-associated strains but was present in one-third of other invasive isolates. Similar to other members of the Neisseriaceae family, the K. kingae differences in invasiveness and tropism for specific body tissues appear to depend on combinations of multiple virulence-associated determinants that are widely distributed throughout the genome. The potential role of the absence of the FrpC protein in the pathogenesis of endocardial invasion deserves further investigation. IMPORTANCE The wide range of clinical severities exhibited by invasive Kingella kingae infections strongly suggests that isolates differ in their genomic contents, and strains associated with life-threatening endocarditis may harbor distinct genomic determinants that result in cardiac tropism and severe tissue damage. The results of the present study show that no single gene discriminated between asymptomatically carried isolates and invasive strains. However, 43 putative genes were significantly more frequent among invasive isolates than among pharyngeal colonizers. In addition, several genes displayed a significant differential distribution among isolates from bacteremia, skeletal system infections, and endocarditis, suggesting that the virulence and tissue tropism of K. kingae are multifactorial and polygenic, depending on changes in the allele content and genomic organization. Further analysis of these putative genes may identify genomic determinants of the invasiveness of K. kingae and its affinity for specific body tissues and potential targets for a future protective vaccine.

SARS-CoV-2 spike antibody concentration in gamma globulin products from high-prevalence COVID-19 countries are transmitted to X-linked agammaglobulinemia patients.

Purpose: Patients with X-linked agammaglobulinemia (XLA) are characterized by humoral impairment and are routinely treated with intravenous immunoglobulin (IVIG). In this study, we aimed to investigate the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in IVIG preparations harvested globally and evaluate the transfer of SARS-CoV-2 antibodies to the XLA patient. Methods: A single-center, prospective cohort study was conducted in the period of November 2020 to November 2022. Clinical and laboratory data, specifically, SARS-CoV-2 spike IgG levels from the serum of 115 IVIG preparations given to 5 XLA patient were collected. Concurrently, SARS-CoV-2 spike IgG levels from the serum of the 5 XLA was collected monthly. Results: Five XLA patients were evaluated within the study period. All were treated monthly with commercial IVIG preparations. A total of 115 IVIG treatments were given over the study period. The origin country and the date of IVIG harvesting was obtained for 111 (96%) of the treatments. Fifty-four IVIG preparations (49%) were harvested during the COVID-19 pandemic of which 76% were positive (>50AU/mL) for SARS-CoV-2 spike antibodies which were subsequently transmitted to the XLA patients in an approximate 10-fold reduction. SARS-CoV2 spike IgG was first detected in IVIG batches that completed their harvest date by September 2021. Positive products were harvested from origin countries with a documented prevalence over 2,000 per 100,000 population. Conclusion: As the prevalence of COVID-19 infections rises, detection of SARS-CoV-2 spike IgG in commercial IVIG products increases and is then transmitted to the patient. Future studies are needed to investigate the neutralizing capabilities of SARS-CoV-2 IgG and whether titer levels in IVIG remain consistent as the incidence of infection and vaccination rates in the population changes.

The risk of serious bacterial infections among young ex-premature infants with fever.

Background and Objectives: To determine the rate of serious-bacterial-infections (SBI) in young ex-premature infants with fever, and to develop a risk-stratification algorithm for these patients. Methods: A retrospective cohort study including all infants who presented to the pediatric emergency department (ED) of a tertiary-care university-hospital between 2010 and 2020 with fever (≥38°C), were born prematurely (<37-weeks), had post-conception age of <52-weeks, and had available blood, urine, or CSF cultures. The rates of SBI by age-of-birth and age-at-visit were calculated and compared to a cohort of matched full-term controls. Results: The study included a total of 290 ex-premature cases and 290 full-term controls. There were 11 cases (3.8%) with an invasive bacterial infection (IBI) of either bacteremia, meningitis or both and only six controls (2.1%) with IBI (p = 0.32). Over 28-days chronologic-age, there were 10 (3.6%) IBIs among cases and no IBIs among the controls (p = 0.02). There were eight (3%) cases and three (1%) controls with IBI who were well-appearing on physical examination (p = 0.19). All eight well-appearing ex-premature infants were under 60-days adjusted-age, seven of whom (88%) were also under 28-days adjusted-age. There were 28 (10.6%) cases and 34 (12%) controls with urinary tract infection (UTI) (p = 0.5). Among cases under 60-days adjusted-age, urinalysis was not reliable to exclude UTI (50% negative). Conclusions: Well-appearing ex-preterm infants have a significant risk for IBI until the adjusted age of 28-days and for UTI until the adjusted age of 60-days. Further studies are needed to evaluate the approach to fever in this unique population.

Non-typhoidal Salmonella bacteremia: comparison of adults and children in a single medical center.

Introduction. Non-typhoidal Salmonella (NTS) bacteremia can cause significant morbidity and mortality. There is high incidence of Salmonellosis in the Middle East, including Israel, but there is a paucity of data on the clinical and epidemiological features of children in comparison to adults.Hypothesis/Gap Statement. Previous studies describing the differences between paediatric and adult populations with Salmonella bacteremia are sparse.Aim. This study's aim was to describe the differences between adults and children with NTS bacteremia.Methodology. All records of patients with NTS bacteremia between 1 January 1998 and 31 July 2020 were reviewed. Data regarding clinical manifestations and laboratory results were extracted from the medical records; records of children (aged <18 years) were compared with those of adults.Results. Records for 137 cases of Salmonella bacteremia (69 adults and 68 children, aged 2 days to 98 years) were reviewed. Seventy nine (58 %) patients had concomitant gastrointestinal symptoms. Fifty-eight (84 %) adults and 13 (19 %) children had underlying conditions (P<0.001). Eighteen patients died, none of whom was a child. Over the study period, most of the children (n=46, 67 %) but only five adults were discharged from the emergency department on their first visit to the ED.Conclusions. The main characteristics of NTS bacteremia in children compared to adults, are higher rates of prior discharge from emergency department, higher rate of gastrointestinal symptoms and better prognosis.

Genetic workup as a complementary tool for the diagnosis of primary complement component deficiencies: a multicenter experience.

Diagnosis of primary complement deficiencies requires a high index of suspicion. Thus, susceptible patients are often underdiagnosed and untreated. Here, we present a multicenter experience with two novel inborn errors of the classical complement system. This is a retrospective multicenter analysis of computerized medical records of children (<18 years) admitted in the period between 2012 and 2018 at Shaare Zedek Medical Center in Jerusalem and Edmond and Lily Safra Children's Hospital, Tel-Hashomer Medical Center, in Ramat Gan, Israel. Patients were genetically diagnosed by a complementary immune workup. We identified 5 patients (3 males) from four different families harboring two novel mutations in the complement components C6-C8. Genetic mutations were identified by whole-exome sequencing or by sequencing of the coding exons of a single gene based on the findings in the immune workup. Clinical manifestations consisted of meningitis with or without meningococcemia. The immune workup demonstrated nearly absent levels of CH50, compatible with a complement pathway defect. Diagnosis delay ranged between 0 and 30 years. CONCLUSION: Awareness of risk factors for primary complement deficiencies, even at the first infectious episode, should facilitate prompt immune and genetic workup, commencing diagnosis and proper treatment for the patient and family. WHAT IS KNOWN: • Deficiencies in the classical terminal complement components increase susceptibility to invasive meningococcal infections. • Recurrent meningococcal infections mandate a diagnostic workup of the complement system. WHAT IS NEW: • Genetic workup can be utilized for prompt diagnosis of complement deficiencies. • High rates of consanguinity, even in the presence of a single meningococcal infection, should promote immune and genetic workups.

Association of post-transplantation anellovirus viral load with kidney transplant rejection in children.

BACKGROUND: Post-transplantation immunosuppressive therapy reduces the risk of graft rejection but raises the risk of infection and malignancy. A biomarker of the level of immunosuppression can be helpful in monitoring immunosuppressive therapy. Inverse correlation between Torque teno virus (TTV) from the Anelloviridae (AV) family load and immune competence was described in previous studies. The aim of this study was to analyze the association between AV family viruses' kinetics and the risk for graft rejection in the first year after kidney transplantation in children. METHODS: The titers of three genera (TTV, TTMDV, and TTMV) from the AV family were monitored by real-time PCR in consecutive samples from children before and after kidney transplantation. RESULTS: Twenty-one children who underwent kidney transplantation were enrolled. Five out of 21 patients experienced acute graft rejection within a year from transplantation. We found that in patients who experienced graft rejection, the median titers of TTV and total AV titers at 5-6 months post-transplantation were lower than in those who did not. Using a threshold determined by ROC analysis, significant differences in TTV and total AV load were found between patients who had or did not have graft rejection (p = 0.002 and 0.004, respectively). No association was found between the dominance of any AV genus titer and the likelihood of rejection. CONCLUSION: This pilot study suggests that children after kidney transplantation with low TTV and total AV titers 5-6 months post-transplantation are at increased risk for graft rejection within a year after transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

B cell repertoire in patients with a novel BTK mutation: expanding the spectrum of atypical X-linked agammaglobulinemia.

X-linked agammaglobulinemia (XLA) is caused by mutations in the Bruton tyrosine kinase) BTK) gene. Affected patients have severely reduced amounts of circulating B cells. Patients with atypical XLA may have residual circulating B cells, and there are few studies exploring these cells' repertoire. We aimed to study the B cell repertoire of a novel hypomorphic mutation in the BTK gene, using the next generation sequencing (NGS) technology. Clinical data was collected from our clinical records. Real-time PCR was used to determine KREC copies, and NGS was used to determine the immunoglobulin (Ig) heavy chain (IgH) repertoire diversity. Both patients had a relatively mild clinical and laboratory phenotype, residual BTK protein expression, and the same novel mutation in the BTK gene, c.1841 T > C, p. L614P. Signal-joint kappa-deleting recombination excision circles (sj-KREC) for both patients were completely absent reflecting lack of naïve B cells. The intron RSS-Kde coding joints (cj) were significantly reduced, reflecting residual replicating B cells. NGS displayed restricted IgH repertoire with highly uneven distribution of clones, especially for Pt2. We report a novel BTK mutation, c.1841 T > C (p. L614P) that is associated with a relatively mild phenotype. We conclude that the IgH repertoire in atypical XLA is restricted with highly uneven distribution of clones. This phenomenon may be explained by extremely reduced to non-existent levels of BTK in B cells. This report sheds further light on atypical cases of XLA.

The impact of pneumococcal conjugate vaccine on the prevalence and severity of hospitalizations for pneumonia in children.

Pneumococcal conjugate vaccines (PCV) were introduced into the Israeli national immunization plan starting with the heptavalent PCV7 in 2009 and then PCV13 in the late 2010. The objective of this study was to determine the vaccines' impact on hospitalization rates for community-acquired pneumonia on the severity of the pneumonia episodes and upon pneumococcal serotype distribution. We retrospectively reviewed all children hospitalized in our institution with pneumonia, aged between 1 and 16 years, between the years 2006 and 2015. Demographic, clinical, and laboratory data between three time periods: pre-PCV, PCV7, and PCV13, were compared. During the study period, 1375 children were hospitalized with pneumonia. A gradual decline in hospitalization rates due to pneumonia was observed starting in 2006 in the pre-PCV period and continued until after the introduction of PCV13. A similar trend was observed in pneumonias with a culture positive for S. pneumoniae. Pleural effusion was observed in 24% of all pneumonias, and this percentage was stable throughout the study period. The average age at hospitalization increased during the study period, as did the average duration of hospital stay. Pneumococcal serotypes included in the vaccine were isolated less frequently during the study and non-vaccine serotypes tended to appear more frequently. Pediatric pneumonia hospitalization rates continued to decline since the introduction of PCV without increasing the frequency of complications. Pneumococcal serotype distribution shifted in parallel. Our findings confirm the efficacy of PCV and support the evidence to include more serotypes in the next generation of PCV.

Coagulase-negative Staphylococci: a rare cause of urinary tract infections in children with consequences on clinical practice.

Isolation of coagulase-negative Staphylococci (CoNS) in urine cultures of children is usually considered a contamination of the sample, except for Staphylococcus saprophyticus in older children. The aim of this study was to describe the characteristics of children in whom CoNS was considered a true urinary pathogen. The medical records of all children aged 0 to 18 years at Shaare Zedek Medical Center between 2013 and 2020 who were diagnosed with CoNS urinary tract infection (UTI) were reviewed for demographic, clinical, and laboratory data. CoNS were identified as the causative organism of UTIs in 30 children, none of whom was bacteremic. Male sex, younger age, and infection with non-S. saprophyticus CoNS were associated with higher risk of pyelonephritis in comparison to cystitis. Eleven (37%) children had previously known or newly diagnosed underlying urinary tract abnormalities. All patients recovered. CoNS were found to be an uncommon urinary pathogen among children but can cause pyelonephritis, especially in young children and in males.Conclusion: The finding of CoNS pyelonephritis requires thorough search for urinary abnormalities.

Comparing blood culture contamination rates by different sampling methods in a paediatric emergency department.

AIM: Blood culture contamination (BCC) can cause unnecessary hospitalisations and inappropriate use of antibiotics. The aim of this study was to find risk factors associated with BCCs in children and to compare contamination rates between open and closed blood culture collection systems. METHODS: Data were prospectively collected regarding blood cultures obtained in the paediatric emergency department from February 26, 2020, to September 30, 2020, based on the method of drawing blood reported by the obtaining physician. A comparison between contaminated and non-contaminated blood cultures was performed. We also compared the composition of the contaminations in the study period to the same period in 2019. RESULTS: A total of 512 blood cultures were included, 33 (6.4%) of which were contaminated. The only parameter that was associated with an increased rate of contamination by 2.34 fold (95% CI 1.1-4.99, P = 0.028) was obtaining blood through an 'open' system, using a syringe connected to a needle in order to draw blood from an open ended needle. The proportion of contaminations originating from oral flora decreased in the study period by 44.7% as compared to the same period in the previous year (13% vs. 23.5%, P = 0.056). CONCLUSIONS: 'Open system' method, which is commonly used in paediatric emergency departments for blood culture obtainment, was associated with an increase in BCC. Adherence to blood cultures obtainment guidelines, even at the price of two different blood tests, is important in order to reduce BCC rates in children.

Dynamics of Invasive Pneumococcal Disease in Israel in Children and Adults in the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Era: A Nationwide Prospective Surveillance.

BACKGROUND: Following 13-valent pneumococcal conjugate vaccine (PCV13) implementation in infants worldwide, overall and vaccine-type invasive pneumococcal disease (IPD) rates declined in children, with variable indirect impact on adults. METHODS: A population-based, prospective, nationwide active surveillance of IPD in Israel, 2004-2019 (for adults ≥18 years, 2009-2019). The 7-valent PCV (PCV7)/PCV13 were implemented in Israel in July 2009/November 2010, respectively, with >90% uptake in children <2 years. The 23-valent pneumococcal polysaccharide vaccine (PPV-23) uptake among those >65 years was ~75%. For pre-PCV episodes with missing serotype, extrapolations were applied. Overall, PCV13 serotypes (VT13) and non-VT13 (NVT) incidence rate ratios (IRRs) comparing pre-PCV (2004-2008), early-PCV (2009-2011), and late-PCV13 (2016-2019) periods were calculated for different age groups. RESULTS: Overall, 8614 IPD cases were recorded. IPD rates declined by 67% in children <5 and 5-17 years, comparing late-PCV13 versus pre-PCV periods (IRR [95% CI]: .33 [.27-.40] and .33 [.21-.50], respectively). For adults, comparing late-PCV13 with early-PCV periods, rates significantly declined by 53% in those aged 18-44, while rates did not decline significantly in other age groups. VT13 rates significantly declined in all ages, with decline rates ranging between 94% in children <5 years and 60% in adults ≥85 years. NVT rates significantly increased in <5-, 50-64-, and ≥65-year age groups. In the late-PCV13 period, serotypes 3, 14, and 19A remained the predominant VT13, while serotypes 8 and 12F emerged as predominant NVTs. CONCLUSIONS: Continuous monitoring of circulating serotypes in all ages demonstrated direct and indirect PCV effects, which are essential for the development of new vaccination strategies.

SARS-CoV-2 antibodies started to decline just four months after COVID-19 infection in a paediatric population.

AIM: We evaluated the prevalence of paediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections using antibody testing and characterised antibody titres by time from exposure. METHODS: This was a single-centre, prospective, cross-sectional cohort study. Patients under 18 years old were eligible to participate if they attended the paediatric emergency department at the tertiary Shaare Zedek Medical Center, Jerusalem, Israel, from 18 October 2020 to 12 January 2021 and required blood tests or intravenous access. SARS-CoV-2 seropositivity and antibody levels were tested by a dual-assay model. RESULTS: The study comprised 1138 patients (56% male) with a mean age of 4.4 years (interquartile range 1.3-11.3). Anti-SARS-CoV-2 antibodies were found in 10% of the patients. Seropositivity increased with age and 41% of seropositive patients had no known exposure. Children under 6 years of age had higher initial antibody levels than older children, followed by a steeper decline. The seropositivity rate did not vary during the study, despite schools re-opening. The findings suggest that children's immunity may start falling 4 months after the initial infection. CONCLUSION: Immunity started falling after just 4 months, and re-opening schools did not affect infection rates. These findings could aid decisions about vaccinating paediatric populations and school closures.

Characterizing the differences between multisystem inflammatory syndrome in children and Kawasaki disease.

To characterize the new SARS-Co-V-2 related multisystem inflammatory syndrome in children (MIS-C) among Israeli children and to compare it with Kawasaki disease (KD). We compared, in two medical centers, the clinical and laboratory characteristics of MIS-C, KD and an intermediate group, which met the case definitions of both conditions. MIS-C patients were older, were more likely to be hypotensive, to have significant gastrointestinal symptoms, lymphopenia and thrombocytopenia and to have non-coronary abnormal findings in their echocardiogram. Lymphopenia was an independent predictor of MIS-C. Most of our MIS-C patients responded promptly to corticosteroid therapy. KD incidence in both centers was similar in 2019 and 2020. Although there is clinical overlap between KD and MIS-C, these are separate entities. Lymphopenia clearly differentiates between these entities. MIS-C patients may benefit from corticosteroids as first-line therapy.

Benign course and clinical features of COVID-19 in hospitalised febrile infants up to 60 days old.

AIM: Minimal data exist regarding the severity of COVID-19 in febrile infants under 60 days old. This multicentre prospective study explored the clinical course and outcomes of this hospitalised patient population, as, to date, the best approach has not been specifically addressed. METHODS: This study focused on the clinical features, laboratory parameters and outcomes of febrile infants up to 60 days old who tested positive for the virus and were hospitalised in Israel from March 2020 to January 2021. The data were extracted from a real-time prospective surveillance network for COVID-19 that includes 20 of the country's 26 hospitals. RESULTS: We identified 75 febrile young infants (60% female) with COVID-19 at a median age of 28 days (range 8-56 days). Of these, 84% had an unremarkable medical history, 29% had respiratory symptoms, and 96% had a mild illness. The Rochester criteria showed that 44% were considered at high-risk for serious bacterial infections, and we found that eight infants actually had concomitant bacterial infections. Outcomes were excellent, and no complications or fatalities were reported. CONCLUSION: The excellent outcomes of young febrile infants with COVID-19 closely resembled other respiratory viral aetiologies of fever in this age group, and there were no fatalities.

COVID-19 in a Subset of Hospitalized Children in Israel.

BACKGROUND: Most pediatric coronavirus disease 2019 (COVID-19) is mild. We assessed nationally severe COVID-19, including pediatric inflammatory multisystem syndrome (PIMS), in hospitalized children. METHODS: An ongoing, prospective, national surveillance was conducted from March 2020 through March 2021, at 20 hospitals treating children <18 years across Israel (~75% of Israeli hospitals). RESULTS: Overall, 1007 cases (439 outpatients and 568 hospitalized) identified represent 0.35% of pediatric COVID-19 nationwide (n = 291 628). Of hospitalized cases, 464 (82%), 48 (8%), and 56 (10%) had mild, moderate/severe, and PIMS disease, respectively. The mean ± SD age was 5.6 ± 6.4 years. In mild, moderate/severe, and PIMS disease, 55%, 23%, and 4% of patients were <1 year old, respectively. Obesity was reported in 1%, 4%, and 13% of patients, respectively (P < .001). The most common symptom was fever in 67%, 60%, and 100%, respectively, whereas respiratory symptoms were documented in 33%, 41%, and 38% of patients, respectively. Lymphopenia was recorded in 25%, 60%, and 86% of cases, respectively. PIMS diagnosis was mainly serology-based (in 59%). Gastrointestinal symptoms, cardiovascular involvement, rash, and conjunctivitis were noted in 82%, 61%, 57%, and 34% of PIMS episodes, respectively. Elevated C-reactive protein (100%), ferritin, troponin, D-dimer, low albumin, and thrombocytopenia were common in PIMS. Echocardiography revealed pathological findings in 33% of patients. PIMS mainstay treatment included corticosteroids (77%) and intravenous immunoglobulin (53%). No mortality was recorded. CONCLUSIONS: At a national level, pediatric COVID-19 is mild, even in hospitalized cases, with only a third presenting with respiratory involvement. PIMS is rare, but necessitates a high index of suspicion, and with suitable treatment prognosis is favorable.

The role of Staphylococcus lugdunensis as a pathogen in children: a multicentre retrospective study.

Introduction: Staphylococcus lugdunensis (SL), a tube coagulase negative Staphylococcus, is known to be pathogenic in adults, causing mainly skin infections.Gap Statement: Previous studies assessing SL's role in paediatric populations are sparse and are mainly limited to case reports.Aim: Present the clinical characteristics consistent with SL infections and its putative role as a pathogen in the paediatric population.Methodology: A retrospective multicentre study was conducted in four paediatric medical centres in Israel. Patients with isolates of SL presenting between 2009-2019 were included.Results: SL was isolated from 40 patients. Average (±SD) age at presentation was 5.9 (±6.2) years, with 22 (55 %) being female. Skin, soft tissue and musculoskeletal infections were the most common (n=20, 50%) followed by ear infections (n=13, 32.5%). Five cases of urine isolates and two isolates from blood culture samples were also reported. Skin abscess was the most common infection among skin and soft tissue isolates, reported in 17 children (85%) with SL being the only pathogen in 15 (75%). Otitis media was the most common ear infection accounting for 12 (92%) of all cases with SL as the only isolate reported in 6 (46%). Five cases of SL isolates from urine specimens were reported, all of which with poor growth of bacteria and normal urinalysis. Two cases of SL growth in blood culture were found in children presenting with signs and symptoms consistent with invasive blood stream infection.Conclusions: In the paediatric population, studied infections caused by SL are increasingly observed. The results of this study highlight its role as a pathogen in soft tissue infections and its putative role in otitis media and invasive blood stream infections. However, the role of SL as an uropathogen was not established.

Quantitative real-time PCR in Borrelia persica tick-borne relapsing fever demonstrates correlation with the Jarisch-Herxheimer reaction.

The purpose of this study is to explore whether a correlation exists between the bacterial load of Borrelia persica in tick-borne relapsing fever (TBRF), established by quantitative real-time PCR, and the development of Jarisch-Herxheimer reaction (JHR) after the initiation of antibiotic treatment. Forty-two blood samples were included in our study. The mean bacterial load, as established by real-time PCR, in patients who developed JHR was significantly greater than in those patients who did not develop JHR (443,293 copies vs. 140,598, p = 0.035). Accordingly, real-time PCR may assist clinicians in identifying patients at higher risk of JHR.